RU-16117

RU-16117
Clinical data
Other names	11α-Methoxyethinylestradiol; 11α-Methoxy-17α-ethynylestradiol; 11α-Methoxy-19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol
Routes of; administration	By mouth[1]
Drug class	Estrogen; Estrogen ether
Identifiers
	IUPAC name (8S,9S,11R,13S,14S,17R)-17-Ethynyl-11-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-diol;
CAS Number	61665-15-4;
PubChem CID	66408;
ChemSpider	59782;
CompTox Dashboard (EPA)	DTXSID60977244 ;
Chemical and physical data
Formula	C21H26O3
Molar mass	326.436 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@]12C[C@H]([C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=C3C=CC(=C4)O)OC;
	InChI InChI=1S/C21H26O3/c1-4-21(23)10-9-17-16-7-5-13-11-14(22)6-8-15(13)19(16)18(24-3)12-20(17,21)2/h1,6,8,11,16-19,22-23H,5,7,9-10,12H2,2-3H3/t16-,17-,18+,19+,20-,21-/m0/s1; Key:MTMZZIPTQITGCY-QHOCJJNXSA-N;

RU-16117 is an estrogen medication which was investigated for the potential treatment of symptoms of estrogen deficiency such as hot flashes and osteoporosis in women but was never marketed.[1] It was developed for use by mouth.[1]

Pharmacology

Pharmacodynamics

RU-16117 is an estrogen, or an agonist of the estrogen receptor (ER).[1][2] In mouse uterine tissue, it shows about 5 to 13% of the affinity of estradiol for the ER and about 1% of the estrogenic activity of estradiol.[2][3][4] Conversely, it shows no affinity for the androgen, progesterone, glucocorticoid, and mineralocorticoid receptors, nor any activities associated with interactions with these receptors.[2][5][3][4] While the association rate of RU-16117 to the ER is the same as that of moxestrol, it dissociates from the ER extremely rapidly at rates of about three times faster than estradiol and about 20 times faster than moxestrol.[1][6] This is similar to the case of estriol, which RU-16117 is described as sharing similarities with.[1][6] RU-16117 is described as a weak or partial estrogen or a mixed estrogen/antiestrogen.[1][2] It has been described as having highly active antiestrogenic activity with very weak uterotrophic activity.[7][2] However, higher doses and/or prolonged administration of RU-16117 have been reported to induce equivalent estrogenic responses relative to estradiol and moxestrol.[1][6]

Relative affinities (%) of RU-16117 and related steroids[5][8][3]
Compound	PR	AR	ER	GR	MR	SHBG	CBG
Estradiol	2.6	7.9	100	0.6	0.13	8.7	<0.1
Estriol	?	?	15	?	?	?	?
Ethinylestradiol	15–25	1–3	112	1–3	<1	?	?
Moxestrol (11β-MeO-EE)	0.8	<0.1	12	3.2	<0.1	<0.2	<0.1
RU-16117 (11α-MeO-EE)	1–3	<1	13	<1	<1	?	?
Values are percentages (%). Reference ligands (100%) were progesterone for the PR, testosterone for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG.

Chemistry

RU-16117, also known as 11α-methoxy-17α-ethynylestradiol (11α-MeO-EE) or as 11α-methoxy-17α-ethynylestra-1,3,5(10)-triene-3,17β-diol, is a synthetic estrane steroid and a derivative of estradiol.[1] It is specifically a derivative of ethinylestradiol (17α-ethynylestradiol) with a methoxy group at the C11α position.[1] The compound is the C11α isomer or C11 epimer of moxestrol (11β-methoxy-17α-ethynylestradiol).[1][9]

References

Raynaud JP, Azadian-Boulanger G, Bouton MM, Colin MC, Faure N, Fernand-Proulx L, Gautray JP, Husson JM, Jolivet A, Kelly P (April 1984). "RU 16117, an orally active estriol-like weak estrogen". J. Steroid Biochem. 20 (4B): 981–93. doi:10.1016/0022-4731(84)90008-6. PMID 6427528.
V. H. T. James; J. R. Pasqualini (22 October 2013). Proceedings of the Fourth International Congress on Hormonal Steroids: Mexico City, September 1974. Elsevier Science. pp. 618–621. ISBN 978-1-4831-4566-2.
Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP (January 1980). "Steroid hormone receptors and pharmacology". J. Steroid Biochem. 12: 143–57. doi:10.1016/0022-4731(80)90264-2. PMID 7421203.
Bouton MM, Raynaud JP (August 1979). "The relevance of interaction kinetics in determining biological response to estrogens". Endocrinology. 105 (2): 509–15. doi:10.1210/endo-105-2-509. PMID 456327.
Ojasoo T, Raynaud JP (November 1978). "Unique steroid congeners for receptor studies". Cancer Res. 38 (11 Pt 2): 4186–98. PMID 359134.
J. Jacob (26 January 2016). Receptors: Proceedings of the 7th International Congress of Pharmacology, Paris, 1978. Elsevier. pp. 261–, 266–267, 274. ISBN 978-1-4831-5796-2.
Kelly PA, Asselin J, Caron MG, Raynaud JP, Labrie F (January 1977). "High inhibitory activity of a new antiestrogen, RU 16117 (11alpha-methoxy ethinyl estradiol), on the development of dimethylbenz(a)anthracene-induced mammary tumors". Cancer Res. 37 (1): 76–81. PMID 187338.
Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors". J. Steroid Biochem. 27 (1–3): 255–69. doi:10.1016/0022-4731(87)90317-7. PMID 3695484.
Alvin M. Kaye; Myra Kaye (22 October 2013). Development of Responsiveness to Steroid Hormones: Advances in the Biosciences. Elsevier Science. pp. 61–. ISBN 978-1-4831-5308-7.

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[pmid6427528-1] Raynaud JP, Azadian-Boulanger G, Bouton MM, Colin MC, Faure N, Fernand-Proulx L, Gautray JP, Husson JM, Jolivet A, Kelly P (April 1984). "RU 16117, an orally active estriol-like weak estrogen". J. Steroid Biochem. 20 (4B): 981–93. doi:10.1016/0022-4731(84)90008-6. PMID 6427528.

[JamesPasqualini2013-2] V. H. T. James; J. R. Pasqualini (22 October 2013). Proceedings of the Fourth International Congress on Hormonal Steroids: Mexico City, September 1974. Elsevier Science. pp. 618–621. ISBN 978-1-4831-4566-2.

[pmid7421203-3] Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP (January 1980). "Steroid hormone receptors and pharmacology". J. Steroid Biochem. 12: 143–57. doi:10.1016/0022-4731(80)90264-2. PMID 7421203.

[pmid456327-4] Bouton MM, Raynaud JP (August 1979). "The relevance of interaction kinetics in determining biological response to estrogens". Endocrinology. 105 (2): 509–15. doi:10.1210/endo-105-2-509. PMID 456327.

[pmid359134-5] Ojasoo T, Raynaud JP (November 1978). "Unique steroid congeners for receptor studies". Cancer Res. 38 (11 Pt 2): 4186–98. PMID 359134.

[Jacob2016-6] J. Jacob (26 January 2016). Receptors: Proceedings of the 7th International Congress of Pharmacology, Paris, 1978. Elsevier. pp. 261–, 266–267, 274. ISBN 978-1-4831-5796-2.

[pmid187338-7] Kelly PA, Asselin J, Caron MG, Raynaud JP, Labrie F (January 1977). "High inhibitory activity of a new antiestrogen, RU 16117 (11alpha-methoxy ethinyl estradiol), on the development of dimethylbenz(a)anthracene-induced mammary tumors". Cancer Res. 37 (1): 76–81. PMID 187338.

[pmid3695484-8] Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors". J. Steroid Biochem. 27 (1–3): 255–69. doi:10.1016/0022-4731(87)90317-7. PMID 3695484.

[KayeKaye2013-9] Alvin M. Kaye; Myra Kaye (22 October 2013). Development of Responsiveness to Steroid Hormones: Advances in the Biosciences. Elsevier Science. pp. 61–. ISBN 978-1-4831-5308-7.